The present invention relates generally to demineralized bone scaffolds and more particularly to demineralized cancellous bone scaffolds for ligament and tendon repair.
Ligaments provide joint stability, guide joint motion, and play an important role in proprioception while tendons transmit forces up to seven times body weight across joints. In the United States alone, there are 150,000 knee injuries involving the anterior cruciate ligament (ACL) and 23,000 injuries to the anterior talofibular ligament in the ankle each year. In addition, damage to the ligaments and tendons in the glenohumeral joints and the spine often lead to long-term musculoskeletal disorders.
Reconstruction with a soft tissue autograft is the most prominent surgical technique for repair of soft connective tissue ruptures. Autografts are preferred due to their biocompatibility and lowered risk for disease transmission. However, graft availability is quite limited and autologous tissue transfer requires the sacrifice of normal tissues. Additionally, in many cases, use of autografts does not regenerate the normal tissue structure, particularly at the interface between the soft connective tissue and the bone. Soft connective tissues join with bone through a complex and distinct interface with four layers. The first is the connective tissue proper, or midsubstance, which consists mostly of a type I collagen matrix. The midsubstance inserts into a layer of fibrocartilage mainly composed of type II collagen rich with proteoglycans. This layer transitions into calcified fibrocartilage layer. The final region is subchondral bone, which contained a mineralized type I collagen matrix. The junction between bone and soft connective tissue has controlled heterogeneity, permitting a gradual manner of load transmission from the hard tissue to the soft tissue in a manner hypothesized to minimize stress and strain concentrations. Prior studies using autografts have shown that using the soft connective tissue proper as the sole graft does not lead to strong biological integration and the re-establishment of the native bone-soft tissue interface. Without such integration, mechanical stability is limited at the joint and the lack of integration can produce higher rates of graft failure. In order to restore the physiological structure and function of the tissue, new strategies must be developed for the treatment of soft connective tissue ruptures.
Tissue engineering has emerged in the past twenty years a promising strategy for soft connective tissue repairs. There have been a number of reports on the use of tissue engineering techniques to regenerate ligaments and tendons. However, most of these studies focus on the midsubstance region and fail to address the regeneration of the interface. To date, collagen fibers, silk fibers, collagen gels and synthetic polymer scaffolds have been utilized to replace the soft tissue portion of the ligament or tendon. One example is a composite collagen fiber-collagen gel scaffold seeded with fibroblasts that does not degrade in vitro and matches many of the mechanical properties of normal ligaments. Unfortunately for many tissues, especially those in the musculoskeletal system, matching the mechanical properties is not sufficient. In order to transmit loads, the construct must successfully integrate with the host tissue and revascularize, processes that are largely governed by the construct's permeability.
Alternatively, bone implants for repairing damaged ligaments and tendons have been made from cortical bone. Examples of such implants are disclosed in U.S. Pat. Nos. 6,090,998 and 6,652,592 (incorporated herein by reference). However, cortical bone is dense with a maximum pore size of 50 μm and implants made from cortical bone do not revascularize to any appreciable extent.
There are a number of design requirements that, once met, may optimize the development of a tissue engineered solution for soft connective tissue rupture. This design requires a biocompatible scaffold that has the mechanical properties to withstand the loading environment. Ideally, the scaffold would be porous to allow more rapid cell incorporation along the surface and through its thickness. The porosity should ensure that cell viability through the thickness is not dependent on vascularization. Tissue ingrowth is vital, but, specifically for this application, the ingrowth must be accompanied by biological integration, so that the normal interface is reformed. Cell behavior is expressly controlled by the interaction with its extracellular environment, in particular the biomaterial surface. The scaffold must guide cells to regenerate of the entire tissue and not simply the soft connective tissue midsubstance.
As can be seen, there is a need for a bone implant or construct that has structural integrity and can easily be integrated into bone and revascularize. It would be desirable if the bone implant allowed for easy attachment to bone and could be custom sized for different applications and patients.